Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model
Flavopiridol is a cyclin-dependent kinase (CDK) inhibitor that promotes cell cycle arrest. We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10...
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| Veröffentlicht in: | Acta dermatovenerologica Croatica 2016-04, Vol.24 (1), p.2-12 |
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| creator | Gokce, Ozlem Dogan Turacli, Irem Ilke Onen, Hacer Erdem, Ozlem Erguven Kayaa, Elif Ekmekci, Abdullah |
| description | Flavopiridol is a cyclin-dependent kinase (CDK) inhibitor that promotes cell cycle arrest. We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10 allograft melanoma tumor model. Flavopiridol and oxaliplatin treated B16F10 cell viability was determined by MTT assay. C57BL6 mice were injected with B16F10 cells and treated with flavopiridol after tumor implantation. BRAF and BCL2L1 mRNA expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR). Caspase 9 and caspase 3/7 activity were determined by activity assay kits. Proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (BCL-2) protein expression levels were analyzed immunohistochemically. Flavopiridol and oxaliplatin decreased cell death. Flavopiridol enhanced caspase 3/7 and caspase 9 activities in vitro and in vivo in a dose dependent manner via the mitochondrial apoptotic pathway. Even though there was a significant increase in Bcl-2 staining, PCNA staining was decreased in flavopiridol-administered mice. Decreased PCNA expression showed antiproliferative effects of flavopiridol which might be the result of cell-cycle arrest. Flavopiridol can be used as a cell cycle inhibitor. |
| format | Article |
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We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10 allograft melanoma tumor model. Flavopiridol and oxaliplatin treated B16F10 cell viability was determined by MTT assay. C57BL6 mice were injected with B16F10 cells and treated with flavopiridol after tumor implantation. BRAF and BCL2L1 mRNA expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR). Caspase 9 and caspase 3/7 activity were determined by activity assay kits. Proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (BCL-2) protein expression levels were analyzed immunohistochemically. Flavopiridol and oxaliplatin decreased cell death. Flavopiridol enhanced caspase 3/7 and caspase 9 activities in vitro and in vivo in a dose dependent manner via the mitochondrial apoptotic pathway. Even though there was a significant increase in Bcl-2 staining, PCNA staining was decreased in flavopiridol-administered mice. Decreased PCNA expression showed antiproliferative effects of flavopiridol which might be the result of cell-cycle arrest. Flavopiridol can be used as a cell cycle inhibitor.</description><identifier>EISSN: 1847-6538</identifier><identifier>PMID: 27149123</identifier><language>eng</language><publisher>Croatia</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Caspases - metabolism ; Cell Culture Techniques ; Disease Models, Animal ; Flavonoids - pharmacology ; Melanoma - metabolism ; Melanoma - pathology ; Mice ; Mice, Inbred C57BL ; Organoplatinum Compounds - pharmacology ; Piperidines - pharmacology ; Proliferating Cell Nuclear Antigen - metabolism ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Tumor Cells, Cultured</subject><ispartof>Acta dermatovenerologica Croatica, 2016-04, Vol.24 (1), p.2-12</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27149123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gokce, Ozlem</creatorcontrib><creatorcontrib>Dogan Turacli, Irem</creatorcontrib><creatorcontrib>Ilke Onen, Hacer</creatorcontrib><creatorcontrib>Erdem, Ozlem</creatorcontrib><creatorcontrib>Erguven Kayaa, Elif</creatorcontrib><creatorcontrib>Ekmekci, Abdullah</creatorcontrib><title>Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model</title><title>Acta dermatovenerologica Croatica</title><addtitle>Acta Dermatovenerol Croat</addtitle><description>Flavopiridol is a cyclin-dependent kinase (CDK) inhibitor that promotes cell cycle arrest. We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10 allograft melanoma tumor model. Flavopiridol and oxaliplatin treated B16F10 cell viability was determined by MTT assay. C57BL6 mice were injected with B16F10 cells and treated with flavopiridol after tumor implantation. BRAF and BCL2L1 mRNA expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR). Caspase 9 and caspase 3/7 activity were determined by activity assay kits. Proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (BCL-2) protein expression levels were analyzed immunohistochemically. Flavopiridol and oxaliplatin decreased cell death. Flavopiridol enhanced caspase 3/7 and caspase 9 activities in vitro and in vivo in a dose dependent manner via the mitochondrial apoptotic pathway. Even though there was a significant increase in Bcl-2 staining, PCNA staining was decreased in flavopiridol-administered mice. Decreased PCNA expression showed antiproliferative effects of flavopiridol which might be the result of cell-cycle arrest. Flavopiridol can be used as a cell cycle inhibitor.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Caspases - metabolism</subject><subject>Cell Culture Techniques</subject><subject>Disease Models, Animal</subject><subject>Flavonoids - pharmacology</subject><subject>Melanoma - metabolism</subject><subject>Melanoma - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Organoplatinum Compounds - pharmacology</subject><subject>Piperidines - pharmacology</subject><subject>Proliferating Cell Nuclear Antigen - metabolism</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Tumor Cells, Cultured</subject><issn>1847-6538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLw0AYRQdBbK3-BZmlm8A8Mo8sa7FaaFCwrsOXzISOTDIxk6l050-3UMXV3Rwu594LNKc6V5kUXM_QdYwfhEitGL1CM6ZoXlDG5-h77eEQBjc6Ezze9CY1NuLlEIYpRBfxwQEu3RSafejN6MDjV5j2X3DErscPVK4pwWUaXW9xaT30oQO8st5HDL3BgN9S3aQJehtS_Cd2qQsjLoOx_gZdtuCjvf3NBXpfP-5Wz9n25WmzWm6zgVE6ZUwJUevTAAnc2NZKY1pic65BU1IIKQSxrKkbmmsuhWxEAZK2lFhOiloo4At0f-4dxvCZbJyqzsXmZHp2q6jSKlesYPSE3v2iqe6sqYbRdTAeq7_X-A9oMmf6</recordid><startdate>201604</startdate><enddate>201604</enddate><creator>Gokce, Ozlem</creator><creator>Dogan Turacli, Irem</creator><creator>Ilke Onen, Hacer</creator><creator>Erdem, Ozlem</creator><creator>Erguven Kayaa, Elif</creator><creator>Ekmekci, Abdullah</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201604</creationdate><title>Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model</title><author>Gokce, Ozlem ; Dogan Turacli, Irem ; Ilke Onen, Hacer ; Erdem, Ozlem ; Erguven Kayaa, Elif ; Ekmekci, Abdullah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-2755b80686a3defe6ddf0e438a810956550e2cbc1483656c59a61f10e309b57a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Caspases - metabolism</topic><topic>Cell Culture Techniques</topic><topic>Disease Models, Animal</topic><topic>Flavonoids - pharmacology</topic><topic>Melanoma - metabolism</topic><topic>Melanoma - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Organoplatinum Compounds - pharmacology</topic><topic>Piperidines - pharmacology</topic><topic>Proliferating Cell Nuclear Antigen - metabolism</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gokce, Ozlem</creatorcontrib><creatorcontrib>Dogan Turacli, Irem</creatorcontrib><creatorcontrib>Ilke Onen, Hacer</creatorcontrib><creatorcontrib>Erdem, Ozlem</creatorcontrib><creatorcontrib>Erguven Kayaa, Elif</creatorcontrib><creatorcontrib>Ekmekci, Abdullah</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Acta dermatovenerologica Croatica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gokce, Ozlem</au><au>Dogan Turacli, Irem</au><au>Ilke Onen, Hacer</au><au>Erdem, Ozlem</au><au>Erguven Kayaa, Elif</au><au>Ekmekci, Abdullah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model</atitle><jtitle>Acta dermatovenerologica Croatica</jtitle><addtitle>Acta Dermatovenerol Croat</addtitle><date>2016-04</date><risdate>2016</risdate><volume>24</volume><issue>1</issue><spage>2</spage><epage>12</epage><pages>2-12</pages><eissn>1847-6538</eissn><abstract>Flavopiridol is a cyclin-dependent kinase (CDK) inhibitor that promotes cell cycle arrest. We aimed to examine the anti-proliferative effects of the flavopiridol and oxaliplatin combination on p16INK4A deficient melanoma cells B16F10 and also its apoptotic effects on a subcutaneously injected B16F10 allograft melanoma tumor model. Flavopiridol and oxaliplatin treated B16F10 cell viability was determined by MTT assay. C57BL6 mice were injected with B16F10 cells and treated with flavopiridol after tumor implantation. BRAF and BCL2L1 mRNA expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR). Caspase 9 and caspase 3/7 activity were determined by activity assay kits. Proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (BCL-2) protein expression levels were analyzed immunohistochemically. Flavopiridol and oxaliplatin decreased cell death. Flavopiridol enhanced caspase 3/7 and caspase 9 activities in vitro and in vivo in a dose dependent manner via the mitochondrial apoptotic pathway. Even though there was a significant increase in Bcl-2 staining, PCNA staining was decreased in flavopiridol-administered mice. Decreased PCNA expression showed antiproliferative effects of flavopiridol which might be the result of cell-cycle arrest. Flavopiridol can be used as a cell cycle inhibitor.</abstract><cop>Croatia</cop><pmid>27149123</pmid><tpages>11</tpages></addata></record> |
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| ispartof | Acta dermatovenerologica Croatica, 2016-04, Vol.24 (1), p.2-12 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects Caspases - metabolism Cell Culture Techniques Disease Models, Animal Flavonoids - pharmacology Melanoma - metabolism Melanoma - pathology Mice Mice, Inbred C57BL Organoplatinum Compounds - pharmacology Piperidines - pharmacology Proliferating Cell Nuclear Antigen - metabolism Skin Neoplasms - metabolism Skin Neoplasms - pathology Tumor Cells, Cultured |
| title | Flavopiridol Induces Apoptosis via Mitochondrial Pathway in B16F10 Murine Melanoma Cells and a Subcutaneous Melanoma Tumor Model |
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